Development of new therapy for canine mammary cancer with recombinant measles virus

Autor: Koichiro Shoji, Misako Yoneda, Tomoko Fujiyuki, Yosuke Amagai, Akane Tanaka, Akira Matsuda, Kikumi Ogihara, Yuko Naya, Fusako Ikeda, Hiroshi Matsuda, Hiroki Sato, Chieko Kai
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Molecular Therapy: Oncolytics, Vol 3, Iss C (2016)
Druh dokumentu: article
ISSN: 2372-7705
DOI: 10.1038/mto.2015.22
Popis: Oncolytic virotherapy is a promising treatment strategy for cancer. We previously generated a recombinant measles virus (rMV-SLAMblind) that selectively uses a poliovirus receptor-related 4 (PVRL4/Nectin4) receptor, but not signaling lymphocyte activation molecule (SLAM). We demonstrated that the virus exerts therapeutic effects against human breast cancer cells. Here, we examined the applicability of rMV-SLAMblind to treating canine mammary cancers (CMCs). We found that the susceptibilities of host cells to rMV-SLAMblind were dependent on canine Nectin-4 expression. Nectin-4 was detected in four of nine CMC cell lines. The rMV-SLAMblind efficiently infected those four Nectin-4-positive cell lines and was cytotoxic for three of them (CF33, CHMm, and CTBm). In vivo experiment showed that the administration of rMV-SLAMblind greatly suppressed the progression of tumors in mice xenografted with a CMC cell line (CF33). Immunohistochemistry revealed that canine Nectin-4 was expressed in 45% of canine mammary tumors, and the tumor cells derived from one clinical specimen were efficiently infected with rMV-SLAMblind. These results suggest that rMV-SLAMblind infects CMC cells and displays antitumor activity in vitro, in xenografts, and ex vivo. Therefore, oncolytic virotherapy with rMV-SLAMblind can be a novel method for treating CMCs.
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